In autoimmune-related diseases the body's own tissues are targeted as a result of a dysfunctional immune response, for example in multiple sclerosis (MS) and in immune-mediated chronic inflammatory diseases that cause inflammation in various tissues, including the intestines (Crohn's disease, ulcerative colitis), in the skin (psoriasis) or of the joints (spectrum of rheumatic diseases). Common to all these disease conditions is that due to the inflammation other disease conditions may occur with an above-average frequency, such as excess weight, high blood pressure, arteriosclerosis, cardiac infarction, and stroke.
Recent knowledge gained in the field of microbiomes has shown that nutrition, the intestinal microbiome, and the local cellular immune response are interconnected. This suggests that dietary measures can have an influence on the cellular immune response and thus on the course of autoimmune diseases and immune-mediated chronic inflammatory diseases
The diversity of the microbiome of the intestine plays an important role. Despite many unanswered questions concerning which components of the microbiome are actually responsible for a differentiated adaptive immune response in the intestinal region, a great amount of empirical information has been collected suggesting that individual types of bacteria and their bacterial metabolites exert a considerable influence on the systemic immune response in connection with autoimmune diseases and immune-mediated chronic inflammatory diseases, for example, in the case of 1 diabetes and Crohn's disease.
It has been found that the intestinal microbiome can be influenced by the type of nutrition consumed and is able to adapt to conditions created by a given kind of food. This means that an intestinal microbiota unfavorable to the immune status of a patient can be changed by taking suitable dietary measures aimed at improving the immune status of the patient.
The intestinal microbiome and dietary habits, such as a high salt intake, have recently been identified as environmental factors in the pathogenesis of multiple sclerosis (MS), an example of an autoimmune-related disease of the central nervous system mediated by T cells. The influence of the intestinal microbiome on chronic inflammatory diseases of the intestines and type 1 diabetes was mentioned above. Distinctive characteristics of the intestinal microbiota have also been detected in patients suffering from type 2 diabetes. Additionally, an association with neurodegenerative diseases (Parkinson's. Alzheimer's) has also been suggested. Recent evidence also shows that there is a major alteration of the intestinal microbiome in the event of renal insufficiency.
An essential role in-autoimmune diseases and in immune-mediated chronic diseases is the action of regulatory T cells (Treg). Treg cells, also known as suppressor T cells, control the activity of the immune system. A deficiency of Treg cells is associated with numerous autoimmune diseases.
Fatty acids have a major influence on the intestinal microbiome as well as on regulatory T cells. It has been reported that long-chain fatty acids have proinflammatory activity. It has now surprisingly been found that short-chain fatty acids have a positive effect on the proliferation and amount of regulatory T cells. This was particularly the case for propionic and butyric acid and their physiologically acceptable salts and esters. Moreover, it has been determined that the targeted administration of short-chain fatty acids with three to six carbon atoms has a positive influence on the development and progression of neuroimmunological diseases with neurodegenerative aspects, like MS.
The use of fumaric acid esters and salts, in particular dimethyl fumarate and salts of monomethyl fumaric acid, for the treatment of MS and psoriasis has been known for years. These agents are effective, but their administration at the threshold of effectiveness is associated with unpleasant side effects, such as gastrointestinal problems and reddening of the skin. The gastrointestinal problems seem to be associated with irritation of the gastric mucosa. In addition, the use of fumarates is associated with leukopenia.
Fumarates are administered—primarily as dimethyl fumarate—in daily doses of usually 2×120 mg (starting dose) or 2×240 mg (maintenance dose). In individual cases a higher dose may be required. Patient doses are often individually adjusted. In MS therapy, dimethyl fumarate is administered as a monotherapy, in psoriasis therapy fumarates are administered as a combination preparation in daily doses of 100 mg to 1.2 g.